Trypanosomes gene expression

FIG. 1.1 Biogenesis of trypanosomatid mRNA. A schematic view of trypanosome gene expression. Mature mRNAs are generated from polycistronic pre-mRNAs via two RNA processing reactions, trans-splicing and polyadenylation. For details, see text. 

Polycistronic transcription units are typical of prokaryotic organisms and of some eukaryotic viruses. Trypanosomes (and nematodes which also trans-splice, see below) represent the only examples of eukaryotes which transcribe their genes in this way. At present, there is no evidence that the various genes encoded in polycistronic transcription units in trypanosomes are related in their function as are operons in bacteria. Likewise, we do not know what the average size of a transcription unit is in trypanosomatids and whether there is any attenuation of transcription in regions that are promoter-distal relative to those that are promoter-proximal. This latter consideration has obvious relevance for the control of gene expression in these organisms. 

I-mediated expression of eukaryotic protein coding genes and they underscore the possibility that some endogenous trypanosome genes, like the VSG and the PARP genes, might indeed be transcribed by RNA polymerase I. 

In addition to elevated AdoMet levels, trypanosomes treated with DFMO in vivo experience a six-fold increase in the activity of protein methylase II but not I or III (55). Protein methylase II specifically methylates carboxyl groups of aspartate and glutamate residues. In mammalian cells, histone methylation may be involved in the condensation of euchromatin to heterochromatin prior to mitosis (56-58), and may therefore have a role in gene expression. Aspartate- and glutamate-rich histones have also been characterized from both T. b. brucei and Crithidia fasciculata making these likely substrates for protein methylase II activity (59,60). 

Vanhamme L, Pays E. Control of gene expression in trypanosomes. Microbiol Rev 1995 ... 

Perry K, A bian N. mRNA processing in the Ttypanosomatidae. Experientia 1991 47 118-128. Das A, Zhang Q, Palenchar JB et al. Trypanosomal TBP functions with the multisubunit transcription factor tSNAP to direct spliced-leader RNA gene expression. Mol Cell Biol 2005 ... 

Antigenic variation (trypanosomes) Varies Nonreciprocal gene conversion Successive expression of different genes encoding the variable surface glycoproteins (VSGs) allows evasion of host immune response. 

Transferrin has been shown to be an essential growth factor for T. brucei bloodstream forms and deprivation of cells of transferrin led to growth arrest (88). A 42 kDa transferrin-binding protein of T. brucei, apparently unrelated to the transferrin receptor described above for Leishmania, has been purified and characterized and its corresponding gene was associated with the VSG expression site (89). This binding protein was attached to the plasma membrane via a glycolipid anchor and thus lacked a cytoplasmic domain. Thus far, it is unclear how such a protein could function as a receptor and interact with the intracellular clathrin-coated vesicles supposed to be involved in receptor-mediated uptake of transferrin by the trypanosomes (76). 

Unlike the situation in trypanosomes, RNAi does not seem to be operative in Leishmania. However, protein expression can be reduced by antisense RNA. This is usually tudiieved by transfection of parasites with an appropriate gene construct. Antisense RNA has been used to reduce the expression of the membrane protease gp63 and the amastigote-specific protein A2. Loss ofeither of the two proteins was shown to reduce parasite virulence, making them attractive drug targets. 

Hoek M, Engstler M, Cross GAM. Expression-site-associated gene 8 (ESAG8) of trypanosome bmcei is apparently essential and accumulates in the nucleolus. J Cell Sci. 

---